Many feminine hygiene and internal cleansing products are used by women predominantly in the form of liquids. More specifically, many women use liquid vaginal douches to irrigate and cleanse the vagina and prevent vaginal infections, for contraception and sterility and to promote abortion ("Feminine Hygiene Products: Why Your Advice Is Needed", U.S. Pharmacist, May, 1986, pp. 20-27, Thomas A. Gossel). Vaginal douche compositions may be made of a variety of compositions. Vinegar is the most common substance used for douching for the purpose of cleansing the vagina. Vinegar consists of approximately 4-6% acetic acid. There is, however, insufficient data to prove conclusively that vinegar is effective in altering the vaginal pH for a sufficient length of time to encourage growth of the normal vaginal flora, and thereby discourage infection.
British Patent Specification No. 1,374,105, published November 13, 1974 and entitled "Effervescent Compositions" describes vaginal douche compositions containing silica gel. The compositions may be tabletted and used as denture cleaners, antacids, analgesing laxatives and vaginal douches. The compositions described contain carbon dioxide and/or oxygen generating materials, e.g., persulphate/perborate mixtures, and optimum pharmaceuticals, diluents, e.g., sodium chloride, chelating agents such as EDTA, surfactants, lubricants, flavorings and odors.
U.S. Pat. No. 3,584,119, issued Jun. 8, 1971 to Daniel B. Langley, describes vaginal douche compositions which contain 3-8 pbw water soluble detergent, sodium dodecylbenzene suphonate, potassium or sodium lauryl sulphate or 2-5 pbw alkali monopersulphate or 5-10 pbw of an alkali metal borate used as aqueous solutions of 5-60 g per liter.
U.S. Pat. No. 3,219,525, issued Nov. 23, 1965 to Samuel G. Berkow et al., describes a pressurized container in which is a solution containing 1.5 to 2.5 mg of a cationic quaternary ammonium germicidal surfactant, 30-60 mg of an antiseptic wetting agent. The resultant composition is an aerosol foam.
It has been reported that when acidic or alkaline solutions were used daily to douche, there were no overall changes in the vaginal pH or the vaginal mucosa. It has also been reported, in turn, demonstrated that during the period of douching, the vaginal pH assumes that of the douche solution. Thirty minutes after douching with an acidic solution, the pH actually becomes alkaline.
Strobino et al. reported that some douches are toxic to sperm, and are therefore used as a contraceptive. In contrast, sodium bicarbonate douches are another type of douche, used to improve sperm survival and thus, to enhance fertility ("Sodium Bicarbonate Douching For Improvement Of The Postcoital Test", Fertility and Sterility, Vol. 33, No. 6, June 1980, pp. 608-612, Ansari, Gould and Ansari).
One type of illness, menstrually occurring toxic shock syndrome (TSS), a severe and sometimes fatal multi-system disease, is associated with infection or colonization by Staphylococcus aureus (S. aureus) bacteria. This disease has been linked to the use of tampons during menstruation. The disease is believed to be caused by toxic shock syndrome toxin-1 (TSST-1), the toxin produced by the majority of staphylococcal strains isolated from menstrual TSS patients.
Subsequent to the publication of reports associating toxic shock syndrome with the use of tampons, a number of investigators undertook studies designed to evaluate the effect of tampons on growth of S. aureus bacteria as well as the effect of tampons on the production of TSST-1 by that bacteria. Early efforts to elucidate the role of tampons in TSS yielded conflicting data. Schlievert et al. (Obstet. Gynecol., Vol. 64, pp. 666-670, November 1984) studied the effect of tampons on S. aureus to evaluate whether or not tampon components increase growth of S. aureus and production of toxic shock syndrome toxin-1. They concluded that, under the test conditions of their study, tampon components provide neither nutrients for growth of toxic shock syndrome S. aureus nor factors that induce production of toxic shock syndrome toxin-1 above control levels. After six hour incubation, some commercially available tampons which were tested were inhibitory to bacterial growth and suppressed toxin production. Others suppressed toxin production but did not inhibit cell growth. One tampon inhibited cell growth but increased the amount of toxin produced. On the other hand, Tierno and Hanna (Contraception, Vol. 31, pp 185-194, 1985) reported that in their experiments tampons did stimulate S. aureus to produce TSST-1.
Reiser et al. (J. Clin. Microbiol., Vol. 25, No. 8, pp 1450-1452, August 1987) thereafter reported the results of tests they conducted to determine the effect of four brands of tampons on production of toxic shock syndrome toxin-1. The amount of air available to the tampons which were tested was limited to that contained in sacs (made from cellulose sausage casing with a molecular weight cut-off of less than 10,000) in which the tampons were enclosed during testing. This method was deemed advantageous in that the limited amount of available air was thought to mimic more closely, than previously used methods, the in vivo condition in the vagina during menstruation with a tampon in place and in that the tampons which were tested were not altered prior to testing. The results of the tests conducted by Reiser et al. indicated that tampons provide increased surface area for the S. aureus bacteria to grow and adequate oxygen for toxin production. No significant inhibition of growth of the staphylococci bacteria or TSST-1 production by any of the tampons tested was noted.
Robbins et al., publishing in J. Clinical Microbiol., Vol. 25, No. 8, pp. 1446-1449, August 1987 at the same time as Reiser et al., reported the effect of 17 commercially available tampons on TSST-1 toxin production using a disk-membrane-agar (DMA) method, with incubation at 37.degree. C. for 19 hours under 5% CO.sub.2 in air. Filter membranes overlaying agar medium (with or without blood) in small petri dishes were spread inoculated with a TSST-1 producing strain of S. aureus. Robbins et al. concluded that the main role of tampons in TSS may be that of providing a fibrous surface for heavy colonization and sufficient air for TSST-1 production. In addition, they found evidence of inhibition of TSST-1 production by additives such as the deodorant/surfactant used in a commercially available deodorant tampon and a decrease in TSST-1 production by inhibiting growth of S. aureus as was observed in the case of a different commercially available tampon. It was thought that both inhibition of TSST-1 production and inhibition of S. aureus growth might prove to be important in reducing the risk of TSS.
S. Notermans et al. (Journal of Food Safety, Vol. 3 (1981), pages 83-88) reported that glyceryl monolaurate, when used in the proportion of 5 g per kg. of meat slurry (pH 6.0-6.2) inhibited toxin productions by Clostridium botulinum type A, type B and type E. This article does not mention Staphylococcus aureus, nor any toxins produced therefrom, nor does it mention feminine hygiene compositions using glyceryl monlaurate or toxic shock syndrome.
In toxic shock syndrome (TSS), whether associated with menstruation or not, the symptoms include fever, hypotension, rash, and desquamation of the skin. TSST-1 is highly associated with menstrual cases but is less often isolated from Staphylococcus aureus strains in non-menstrual cases of the illness. Since TSST-1 can induce many clinical features of TSS in the rabbit and other species, it is generally thought to be the causative toxin in TSS (Schlievert, "Staphylococcal Enterotoxin B and Toxic Shock Syndrome Toxin-1 Are Significantly Associated With Non-menstrual TSS", The Lancet, Vol. 1 (8490), May 17, 1986). However, Garbe (Garbe, Arko, Reingold et al., "Staphylococcus aureus isolates from patients with non-menstrual toxic shock syndrome: Evidence for additional toxins", JAMA, 1985, Vol. 253; pp. 2538-42) noted that many TSS isolates from nonmenstrual cases did not express TSST-1 though they did cause TSS-like symptoms in a rabbit model. Of the toxins formed by S. aureus nonmenstrual isolates, TSST-1 was produced by 40% of those reported by Schlievert, 1986.
The production of TSST-1 by S. aureus has predominantly been associated with menstrual TSS related to tampon usage. Experiments were initiated to determine whether one could minimize or interrupt the production of TSST-1 within absorbent fibrous materials. Unexpectedly, a group of compounds were identified which is described in copending U.S. patent applications Ser. No. 343,965, filed Apr. 27, 1989 and Ser. No. 316,742 filed Apr. 27, 1990, which are hereby incorporated herein by reference.
However, there is a need to find a douche composition which is able to combat the production of TSST-1 by Staphylococcus aureus within the vaginal cavity.